SPOT is not intended to be used to predict true causal variants or to statistically interpret the results of GWAS. Furthermore, the problem of establishing such predictive properties for SPOT, such as through assessments of false-positive rates and receiver operating characteristics, is ill posed due to the fact that one of the core features of SPOT is that it allows the investigator to prioritize specific genes and genomic regions. Since these parameters depend on the particular biological priorities of the investigator, the general predictive properties of SPOT cannot be established. Another issue is the extreme diversity of phenotype and disease. For example, few genetic associations for psychiatric disease have been validated by replication in independent samples (37). Therefore, in order to conclude that any evidence of correlation between the biological information used by SPOT and existing confirmed genotype–phenotype associations would transfer to the prediction of true genetic associations for psychiatric disease, one would have to make the unlikely assumption that the underlying genetic structure of psychiatric disease shares substantial common elements with other types of human disease in general.
